Human Insulin-like Growth Factor-1, (UniProtKB entry P05019, IGF1_human, (SEQ ID NO:1)) also known as somatomedin C and somatomedin A, is in its mature form a 70 amino acid polypeptide (SEQ ID NO:2), that shares large stretches of sequence identity and high structural homology with IGF-2 and insulin (Rinderknecht, E. and Humbel, R. E., Proc. Natl. Acad. Sci. USA 73 (1976) 2365-2369; Rinderknecht, E. and Humbel, R. E., J. Biological Chemistry 253 (1978) 2769-2776). Human IGF-2 is present in human serum with a 500-fold molar excess over IGF-1 (Jones, J. I. and Clemmons, D. R., Endocr. Rev. 16 (1995) 3-34). The higher serum concentration of IGF-2 and its sequence homology with IGF-1 are major obstacles to the specific immunological detection of IGF-1.
Similar to insulin, the IGF-1 polypeptide chain can be divided into domains. IGF-1 comprises four domains, B (amino acid residues 1-29), C (30-41), A (42-62) and D (63-70), respectively. Domains A and B are structural homologs of insulin B and A chains, respectively, domain C is analogous to the connecting peptide of proinsulin, while the D-domain has no counterpart in insulin.
As summarized by Manes S., et al., J. Endocrinol. 154 (1997) 293-302, IGF-1 is thought to mediate the growth-promoting activity of growth hormone (GH) (Sara, V. R. and Hall, K., Physiol Rev. 70 (1990) 591-614). It is also considered critical in local control of cell growth, differentiation and survival in a variety of cell types through a paracrine or autocrine pathway (Jones J. I. and Clemmons, D. R., Endocrin. Rev. 16 (1995) 3-34). The putative receptor for IGF-1, the type-1 IGF receptor (IGF-1R) (Ullrich, A., et al., EMBO J., 5 (1986) 2503-2512), has been proposed to play a key role in tumorigenesis (Sell, C., et al., Proc. Natl. Acad. Sci. USA 90 (1993) 11217-11221). There is ample evidence indicating that many tumors express IGF-1R and produce and secrete IGF-1 or IGF-2 to the extracellular milieu (Baserga, R., Cell 79 (1994) 927-930; Werner, H., et al., Int. J. Biochem. Cell Biol. 27 (1995) 987-994), thereby promoting continuous cell growth in an autocrine fashion.
Both IGF-1 and IGF-2 are expressed in numerous tissues and cell types and may have autocrine, paracrine and endocrine functions. Mature IGF-1 and IGF-2 are highly conserved between the human, bovine and porcine proteins (100% identity), and also exhibit cross-species activity. The IGFL (insulin-like growth factor-like) family includes four small (˜11 kDa) family members in humans and one in mouse.